Induction of tumor cell apoptosis by taurine Schiff base copper complex is associated with the inhibition of proteasomal activity.
Schiff bases have been intensively investigated due to their antibacterial and antitumor properties. Copper is a cofactor essential for the tumor angiogenesis processes, whereas other transition metals are not. Consistently, high serum or tissue levels of copper were found in many types of human cancer including breast, prostate, colon, lung, and brain, supporting the idea that copper could be used as a novel selective target for cancer therapies. In the current study we hypothesize that a synthetic taurine Schiff base copper complex (Compound 1) could suppress tumor cell growth via the direct inhibition of proteasomal activity. Compound 1 potently inhibits the activity of purified 20S and 26S proteasome in human breast cancer MDA-MB-231 and leukemia Jurkat T cells. Inhibition of tumor cellular proteasomal activity by Compound 1 results in the accumulation of ubiquitinated protein and the proteasome target proteins p27 and Bax, followed by the induction of apoptosis. Our results strongly suggest that taurine Schiff base copper complexes, as potent proteasome inhibitors, have great potential to be developed into novel anticancer drugs.
Zhang
Xia
X
Key Laboratory of Marine Chemistry Engineering and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, PR China.
Bi
Caifeng
C
Fan
Yuhua
Y
Cui
Qiuzhi
Q
Chen
Di
D
Xiao
Yan
Y
Dou
Q Ping
QP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D012545:Schiff Bases / Q000737:chemistry / Q000494:pharmacology*; D013654:Taurine; D054875:Ubiquitination / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; C494826:BAX protein, human; D061988:Proteasome Inhibitors; D012545:Schiff Bases; D051028:bcl-2-Associated X Protein; D013654:Taurine; D003300:Copper; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease